Table 1.
Clinical, Pathological, and Molecular Characteristics of Colorectal Cancer Cases According to Fusobacterium nucleatum DNA Amount in Tumor Tissue
| F. nucleatum DNA in tumor tissue | |||||
|---|---|---|---|---|---|
| Characteristic* | All cases (N = 933) | Negative (N = 805) | Low (N = 64) | High (N = 64) | P value† |
| Sex | 0.61 | ||||
| Female (NHS) | 513 (55%) | 439 (55%) | 35 (55%) | 39 (61%) | |
| Male (HPFS) | 420 (45%) | 366 (45%) | 29 (45%) | 25 (39%) | |
| Mean age ± SD (years) | 69.1 ± 8.8 | 69.0 ± 8.9 | 70.6 ± 8.6 | 68.9 ± 8.0 | 0.37 |
| Year of diagnosis | 0.13 | ||||
| 1995 or before | 300 (32%) | 268 (33%) | 13 (20%) | 19 (30%) | |
| 1996–2000 | 307 (33%) | 264 (33%) | 20 (31%) | 23 (36%) | |
| 2001–2012 | 326 (35%) | 273 (34%) | 31 (48%) | 22 (34%) | |
| Family history of colorectal cancer in first-degree relative(s) | 0.69 | ||||
| Absent | 730 (79%) | 627 (78%) | 51 (81%) | 52 (83%) | |
| Present | 195 (21%) | 172 (22%) | 12 (19%) | 11 (17%) | |
| Tumor location | 0.084 | ||||
| Cecum | 166 (18%) | 135 (18%) | 16 (25%) | 15 (23%) | |
| Ascending to transverse colon | 300 (32%) | 253 (32%) | 23 (36%) | 24 (38%) | |
| Descending to sigmoid colon | 276 (30%) | 251 (30%) | 10 (16%) | 15 (23%) | |
| Rectum | 187 (20%) | 162 (20%) | 15 (23%) | 10 (16%) | |
| Tumor differentiation | < 0.0001 | ||||
| Well to moderate | 846 (91%) | 745 (93%) | 52 (83%) | 49 (77%) | |
| Poor | 86 (9.2%) | 60 (7.5%) | 11 (17%) | 15 (23%) | |
| AJCC disease stage | 0.090 | ||||
| I | 201 (23%) | 184 (25%) | 8 (14%) | 9 (15%) | |
| II | 284 (33%) | 235 (32%) | 22 (38%) | 27 (44%) | |
| III | 251 (29%) | 214 (29%) | 22 (38%) | 15 (25%) | |
| IV | 127 (15%) | 111 (15%) | 6 (10%) | 10 (16%) | |
| MSI status | < 0.0001 | ||||
| Non-MSI-high | 750 (83%) | 669 (86%) | 42 (69%) | 39 (61%) | |
| MSI-high | 156 (17%) | 112 (14%) | 19 (31%) | 25 (39%) | |
| CIMP status | < 0.0001 | ||||
| Low/negative | 708 (82%) | 627 (84%) | 46 (78%) | 35 (58%) | |
| High | 160 (18%) | 122 (16%) | 13 (22%) | 25 (42%) | |
| Mean LINE-1 methylation level ± SD (%) | 62.5 ± 9.6 | 62.2 ± 9.6 | 63.0 ± 9.3 | 64.8 ± 9.9 | 0.099 |
| KRAS mutation | 0.33 | ||||
| Wild-type | 536 (59%) | 466 (59%) | 30 (51%) | 40 (63%) | |
| Mutant | 370 (41%) | 318 (41%) | 29 (49%) | 23 (37%) | |
| BRAF mutation | 0.0009 | ||||
| Wild-type | 776 (85%) | 680 (86%) | 52 (85%) | 44 (69%) | |
| Mutant | 138 (15%) | 109 (14%) | 9 (15%) | 20 (31%) | |
| PIK3CA mutation | 0.95 | ||||
| Wild-type | 715 (84%) | 618 (84%) | 46 (82%) | 51 (84%) | |
| Mutant | 139 (16%) | 119 (16%) | 10 (18%) | 10 (16%) | |
| Neoantigen loads | 0.0002 | ||||
| Q1 (lowest) | 107 (25%) | 94 (26%) | 6 (19%) | 7 (23%) | |
| Q2 | 105 (25%) | 91 (25%) | 10 (31%) | 4 (13%) | |
| Q3 | 106 (25%) | 100 (28%) | 4 (13%) | 2 (6.7%) | |
| Q4 (highest) | 106 (25%) | 77 (21%) | 12 (37%) | 17 (57%) | |
| Exome wide tumor mutation burden | 0.001 | ||||
| Q1 (lowest) | 107 (25%) | 95 (26%) | 6 (19%) | 6 (20%) | |
| Q2 | 106 (25%) | 95 (26%) | 7 (22%) | 4 (13%) | |
| Q3 | 105 (25%) | 95 (26%) | 7 (22%) | 3 (10%) | |
| Q4 (highest) | 106 (25%) | 77 (21%) | 12 (38%) | 17 (57%) | |
| Median stromal CD3+ cell density (IQR) (cells/mm2) | 145 (22–493) | 162 (26–538) | 94 (6.8–302) | 71 (6.9–238) | 0.0002‡ |
| Median stromal CD3+CD4+ cell density (IQR) (cells/mm2) | 76 (3.8–361) | 84 (4.9–392) | 44 (0–207) | 37 (0–164) | 0.0007‡ |
| Median stromal CD3+CD8+ cell density (IQR) (cells/mm2) | 10 (0–54) | 10 (0–56) | 11 (0–56) | 9.3 (0–34) | 0.69‡ |
| Median stromal CD3+CD4+CD45RO+ cell density (IQR) (cells/mm2) | 57 (0–287) | 67 (2.9–329) | 33 (0–162) | 24 (0–134) | 0.0006‡ |
| Median stromal CD3+CD4+CD45RO− cell density (IQR) (cells/mm2) | 7.2 (0–48) | 7.7 (0–51) | 0 (0–38) | 4.2 (0–26) | 0.034‡ |
| Median stromal overall macrophage density (IQR) (cells/mm2) | 871 (489–1428) | 859 (479–1399) | 966 (579–1667) | 894 (609–1477) | 0.33‡ |
| Median stromal M1-like macrophage density (IQR) (cells/mm2) | 175 (65–398) | 170 (62–379) | 202 (68–548) | 192 (85–452) | 0.14‡ |
| Median stromal M2-like macrophage density (IQR) (cells/mm2) | 192 (69–429) | 192 (69–435) | 191 (69–435) | 196 (63–431) | 0.33‡ |
| Bifidobacterium genus DNA in tumor tissue | |||||
| Negative | 631 (71%) | 556 (72%) | 38 (64%) | 37 (62%) | 0.094 |
| Low | 128 (14%) | 104 (14%) | 9 (15%) | 15 (25%) | |
| High | 128 (14%) | 108 (14%) | 12 (20%) | 8 (13%) | |
Percentage indicates the proportion of patients with a specific clinical, pathologic, or molecular characteristic among all patients or in strata of F. nucleatum DNA amount.
To compare categorical data between subgroups classified by F. nucleatum DNA amount, the chi-square test was performed, unless otherwise noted. To compare continuous variables, an analysis of variance was performed.
To assess associations between F. nucleatum DNA amount (continuous) and densities of T cell subsets and macrophage (continuous), the Spearman’s correlation test was performed.
Abbreviations: AJCC, American Joint Committee on Cancer; CIMP, CpG island methylator phenotype; HPFS, Health Professionals Follow-up Study; IQR, interquartile range; LINE-1, long-interspersed nucleotide element-1; MSI, microsatellite instability; NHS, Nurses’ Health Study; SD, standard deviation.